Our overall goal is to improve the efficiency of clinical trials of new cancer therapies by enhancing the effectiveness of quantitative PET/CT imaging of tumor response. In this renewal application, we seek to deploy and validate in multi-center clinical trials the quantitative PET imaging tools and methods that we have developed within the Quantitative Imaging Network (QIN) during the current project period. While quantitative PET imaging is a uniquely powerful tool to assess response to potential cancer therapies, it is also subject to several sources of bias and variability that degrade study power. In addition, multi-center studies are needed to increase patient accrual rates, even in early-phase studies. These multi-center studies can confound quantitative accuracy, further reducing study power, leading to missed opportunities in evaluating new therapies To accelerate the evaluation of cancer therapies using quantitative PET imaging we have three distinct and linked aims: (1) Develop and implement a unified database and imaging platform that enables feasible deployment of our phantoms and software tools. (2) Extend our quantitative FDG PET imaging tools to FLT (proliferation) and FES (receptor status) in multicenter studies. (3) Prospectively test the integration of the above tools and methods in a clinical trial that uses 18F-FES PET imaging to evaluate new breast cancer therapies. These approaches can be readily extended to other cancers using quantitative PET imaging. The prospective testing of quantitative PET imaging tools in multisite clinical trials is an essential step towards adoption. In turn this will help accelerate the effective evaluation of improved cancer therapies by quantitative imaging, which will benefit investigators, clinicians, and cancer patients.